OVERALL PROJECT SUMMARY/ABSTRACT The mission of Case Comprehensive Cancer Center (Case CCC), now in its 27th grant year, is to promote a coordinated, translational research-oriented culture of scientific discovery applied to human cancers, that improves cancer detection, prevention, treatment, cure, and survivorship in Cleveland, Northeast Ohio and around the world, and to disseminate its advances to patients and populations. The Center provides leadership and oversight of collaboration for basic cancer research oriented toward identification of novel therapeutic targets; prevention, control and population research; therapeutic and non-therapeutic clinical research across the disease spectrum; and community outreach. These accomplishments include examples of practice changing impact within the catchment area and nationally. The Center coordinates all aspects of cancer research in Cleveland and Northern Ohio, including activities of the affiliate institutions of Case Western Reserve University, Cleveland Clinic, and University Hospitals. The Center provides opportunities to participate in clinical trials to almost 16,000 cancer patients (over 62% of cancer cases in the catchment area) who are newly diagnosed annually in the region. The Case CCC is organized around 7 Research Programs, 13 Shared Resources, and a clinical and behavioral cancer research infrastructure that prioritizes innovative translational research and investigator-initiated clinical trials that cut across the Research Programs. The Case CCC includes 279 members (172 Full, 32 Associate, and 75 Clinical) from 7 schools and 68 academic departments who actively participate in Center activities including Program and Shared Resource meetings and retreats, and leadership committees, each promoting a transdisciplinary approach that facilitates discovery and clinical application. The cancer focus of the Center is exceptional, with over $77M in direct funding and over $26M in direct NCI funding. Institutional commitment is also exceptional, codified through an updated Memorandum of Understanding. The consortium members will provide over $128M of internal funds for cancer research in the next grant cycle. The Case CCC and its affiliate institutions have established an outstanding infrastructure that enables its members to improve the prevention, diagnosis, and treatment of cancer through discovery, implementation and dissemination, and collaborative transdisciplinary research while providing state-of-the-art care and treatment to cancer patients and their families. The Case CCC yields tangible benefits as an active partner with the NCI by supporting cancer relevant scientific research with direct benefit to patients and the general public.